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Dexmethylphenidate

July 24, 2017
Common Name

Dexmethylphenidate Description

Dexmethylphenidate is only found in individuals that have used or taken this drug. It is the dextrorotary form of methylphenidate. It is used for treatment of Attention Deficit Hyperactivity Disorder (ADHD). Methylphenidate blocks dopamine uptake in central adrenergic neurons by blocking dopamine transport or carrier proteins. Methylphenidate acts at the brain stem arousal system and the cerebral cortex and causes increased sympathomimetic activity in the central nervous system.Methylphenidate is a catecholamine reuptake inhibitor that indirectly increases catecholaminergic neurotransmission by inhibiting the dopamine transporter (DAT) and norepinephrine transporter (NET), which are responsible for clearing catecholamines from the synapse, particliarly in the striatum and meso-limbic system. Structure

MOLSDF3D-SDFPDBSMILESInChI View 3D Structure

Synonyms

Value Source (+)-threo-MethylphenidateChEBI D-threo-MethylphenidateChEBI DexmethylphenidatumChEBI DexmetilfenidatoChEBI Methyl (R)-phenyl[(R)-piperidin-2-yl]acetateChEBI (+)-threo-Methylphenidic acidGenerator Dexmethylphenidic acidGenerator D-threo-Methylphenidic acidGenerator Methyl (R)-phenyl[(R)-piperidin-2-yl]acetic acidGenerator Dexmethylphenidate hydrochlorideMeSH Focalin XRMeSH Hydrochloride, dexmethylphenidateMeSH XR, FocalinMeSH FocalinMeSH

Chemical Formlia

C14H19NO2 Average Molecliar Weight

233.3062 Monoisotopic Molecliar Weight

233.141578857 IUPAC Name

methyl (2R)-2-phenyl-2-[(2R)-piperidin-2-yl]acetate Traditional Name

dexmethylphenidate CAS Registry Number

40431-64-9 SMILES

COC(=O)[C@@H]([C@H]1CCCCN1)C1=CC=CC=C1

InChI Identifier

InChI=1S/C14H19NO2/c1-17-14(16)13(11-7-3-2-4-8-11)12-9-5-6-10-15-12/h2-4,7-8,12-13,15H,5-6,9-10H2,1H3/t12-,13-/m1/s1

InChI Key

DUGOZIWVEXMGBE-CHWSQXEVSA-N Chemical Taxonomy Description

This compound belongs to the class of chemical entities known as aralkylamines. These are alkylamines in which the alkyl group is substituted at one carbon atom by an aromatic hydrocarbyl group. Kingdom

Chemical entities Super Class

Organic compounds Class

Organic nitrogen compounds Sub Class

Organonitrogen compounds Direct Parent

Aralkylamines Alternative Parents

  • Piperidines
  • Benzene and substituted derivatives
  • Methyl esters
  • Amino acids and derivatives
  • Monocarboxylic acids and derivatives
  • Dialkylamines
  • Azacyclic compounds
  • Organopnictogen compounds
  • Organic oxides
  • Hydrocarbon derivatives
  • Carbonyl compounds

    • Substituents

  • Aralkylamine
  • Monocyclic benzene moiety
  • Piperidine
  • Benzenoid
  • Methyl ester
  • Amino acid or derivatives
  • Carboxylic acid ester
  • Carboxylic acid derivative
  • Secondary aliphatic amine
  • Monocarboxylic acid or derivatives
  • Secondary amine
  • Azacycle
  • Organoheterocyclic compound
  • Organopnictogen compound
  • Organooxygen compound
  • Hydrocarbon derivative
  • Carbonyl group
  • Organic oxygen compound
  • Organic oxide
  • Aromatic heteromonocyclic compound

    • Molecliar Framework

    Aromatic heteromonocyclic compounds External Descriptors

  • methyl phenyl(piperidin-2-yl)acetate (CHEBI:51860 )

    • Ontology Status

    Expected but not Quantified Origin

  • Drug

    • Biofunction

    Not Available Application

  • Pharmaceutical

    • Cellliar locations

  • Membrane

    • Physical Properties State

    Solid Experimental Properties

    Property Value Reference Melting PointNot AvailableNot Available Boiling PointNot AvailableNot Available Water SolubilityNot AvailableNot Available LogPNot AvailableNot Available

    Predicted Properties

    Property Value Source Water Solubility0.18 mg/mLALOGPS logP1.47ALOGPS logP2.25ChemAxon logS-3.1ALOGPS pKa (Strongest Basic)9.09ChemAxon Physiological Charge1ChemAxon Hydrogen Acceptor Count2ChemAxon Hydrogen Donor Count1ChemAxon Polar Surface Area38.33 Å2ChemAxon Rotatable Bond Count4ChemAxon Refractivity66.73 m3·mol-1ChemAxon Polarizability26.23 Å3ChemAxon Number of Rings2ChemAxon Bioavailability1ChemAxon Rlie of FiveYesChemAxon Ghose FilterYesChemAxon Vebers RlieYesChemAxon MDDR-like RlieYesChemAxon

    Spectra Spectra

    Spectrum Type Description Splash Key Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 10V, PositiveNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 20V, PositiveNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 40V, PositiveNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 10V, NegativeNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 20V, NegativeNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 40V, NegativeNot Available

    Biological Properties Cellliar Locations

  • Membrane

    • Biofluid Locations

  • Blood
  • Urine

    • Tissue Location

    Not Available Pathways

    Not Available Normal Concentrations

    Biofluid Status Value Age Sex Condition Reference Details BloodExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB06701

  • 21059682

    • details UrineExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB06701

  • 21059682

    • details

    Abnormal Concentrations

    Not Available Predicted Concentrations

    Biofluid Value Original age Original sex Original condition Comments Blood0-4 uMAdlit (>18 years old)BothNormalPredicted based on drug qualities Blood0-2 umol/mmol creatinineAdlit (>18 years old)BothNormalPredicted based on drug qualities

    Associated Disorders and Diseases Disease References

    None Associated OMIM IDs

    None External Links DrugBank ID

    DB06701 DrugBank Metabolite ID

    Not Available Phenol Explorer Compound ID

    Not Available Phenol Explorer Metabolite ID

    Not Available FoodDB ID

    Not Available KNApSAcK ID

    Not Available Chemspider ID

    135807 KEGG Compound ID

    Not Available BioCyc ID

    Not Available BiGG ID

    Not Available Wikipedia Link

    Dexmethylphenidate NuGOwiki Link

    HMDB15647 Metagene Link

    HMDB15647 METLIN ID

    Not Available PubChem Compound

    154101 PDB ID

    Not Available ChEBI ID

    51860

    Product: Bindarit

    References Synthesis Reference Not Available Material Safety Data Sheet (MSDS) Not Available General References Not Available

    Enzymes

    General function:
    Involved in monooxygenase activity
    Specific function:
    Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants.
    Gene Name:
    CYP2D6
    Uniprot ID:
    P10635
    Molecular weight:
    55768.94
    References
    1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
    General function:
    Involved in neurotransmitter:sodium symporter activity
    Specific function:
    Amine transporter. Terminates the action of dopamine by its high affinity sodium-dependent reuptake into presynaptic terminals.
    Gene Name:
    SLC6A3
    Uniprot ID:
    Q01959
    Molecular weight:
    68494.255
    References
    1. Markowitz JS, Patrick KS: Differential pharmacokinetics and pharmacodynamics of methylphenidate enantiomers: does chirality matter? J Clin Psychopharmacol. 2008 Jun;28(3 Suppl 2):S54-61. doi: 10.1097/JCP.0b013e3181733560. [PubMed:18480678 ]
    2. Ding YS, Fowler JS, Volkow ND, Dewey SL, Wang GJ, Logan J, Gatley SJ, Pappas N: Chiral drugs: comparison of the pharmacokinetics of [11C]d-threo and L-threo-methylphenidate in the human and baboon brain. Psychopharmacology (Berl). 1997 May;131(1):71-8. [PubMed:9181638 ]
    3. Davids E, Zhang K, Tarazi FI, Baldessarini RJ: Stereoselective effects of methylphenidate on motor hyperactivity in juvenile rats induced by neonatal 6-hydroxydopamine lesioning. Psychopharmacology (Berl). 2002 Feb;160(1):92-8. Epub 2001 Dec 18. [PubMed:11862378 ]
    4. Volkow ND, Fowler JS, Gatley SJ, Dewey SL, Wang GJ, Logan J, Ding YS, Franceschi D, Gifford A, Morgan A, Pappas N, King P: Comparable changes in synaptic dopamine induced by methylphenidate and by cocaine in the baboon brain. Synapse. 1999 Jan;31(1):59-66. [PubMed:10025684 ]
    5. Wayment HK, Deutsch H, Schweri MM, Schenk JO: Effects of methylphenidate analogues on phenethylamine substrates for the striatal dopamine transporter: potential as amphetamine antagonists? J Neurochem. 1999 Mar;72(3):1266-74. [PubMed:10037500 ]
    6. Dresel SH, Kung MP, Huang X, Plossl K, Hou C, Shiue CY, Karp J, Kung HF: In vivo imaging of serotonin transporters with [99mTc]TRODAT-1 in nonhuman primates. Eur J Nucl Med. 1999 Apr;26(4):342-7. [PubMed:10199939 ]
    7. Volkow ND, Wang GJ, Fowler JS, Fischman M, Foltin R, Abumrad NN, Gatley SJ, Logan J, Wong C, Gifford A, Ding YS, Hitzemann R, Pappas N: Methylphenidate and cocaine have a similar in vivo potency to block dopamine transporters in the human brain. Life Sci. 1999;65(1):PL7-12. [PubMed:10403500 ]
    8. Izenwasser S, Coy AE, Ladenheim B, Loeloff RJ, Cadet JL, French D: Chronic methylphenidate alters locomotor activity and dopamine transporters differently from cocaine. Eur J Pharmacol. 1999 Jun 4;373(2-3):187-93. [PubMed:10414438 ]
    9. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
    10. Tatsumi M, Groshan K, Blakely RD, Richelson E: Pharmacological profile of antidepressants and related compounds at human monoamine transporters. Eur J Pharmacol. 1997 Dec 11;340(2-3):249-58. [PubMed:9537821 ]
    11. Viggiano D, Vallone D, Sadile A: Dysfunctions in dopamine systems and ADHD: evidence from animals and modeling. Neural Plast. 2004;11(1-2):97-114. [PubMed:15303308 ]
    12. Tilley MR, Gu HH: The effects of methylphenidate on knockin mice with a methylphenidate-resistant dopamine transporter. J Pharmacol Exp Ther. 2008 Nov;327(2):554-60. doi: 10.1124/jpet.108.141713. Epub 2008 Aug 12. [PubMed:18698001 ]

    Transporters

    General function:
    Involved in neurotransmitter:sodium symporter activity
    Specific function:
    Amine transporter. Terminates the action of noradrenaline by its high affinity sodium-dependent reuptake into presynaptic terminals.
    Gene Name:
    SLC6A2
    Uniprot ID:
    P23975
    Molecular weight:
    69331.42
    References
    1. Markowitz JS, Patrick KS: Differential pharmacokinetics and pharmacodynamics of methylphenidate enantiomers: does chirality matter? J Clin Psychopharmacol. 2008 Jun;28(3 Suppl 2):S54-61. doi: 10.1097/JCP.0b013e3181733560. [PubMed:18480678 ]
    2. Ding YS, Fowler JS, Volkow ND, Dewey SL, Wang GJ, Logan J, Gatley SJ, Pappas N: Chiral drugs: comparison of the pharmacokinetics of [11C]d-threo and L-threo-methylphenidate in the human and baboon brain. Psychopharmacology (Berl). 1997 May;131(1):71-8. [PubMed:9181638 ]
    3. Davids E, Zhang K, Tarazi FI, Baldessarini RJ: Stereoselective effects of methylphenidate on motor hyperactivity in juvenile rats induced by neonatal 6-hydroxydopamine lesioning. Psychopharmacology (Berl). 2002 Feb;160(1):92-8. Epub 2001 Dec 18. [PubMed:11862378 ]
    4. Yang L, Wang YF, Li J, Faraone SV: Association of norepinephrine transporter gene with methylphenidate response. J Am Acad Child Adolesc Psychiatry. 2004 Sep;43(9):1154-8. [PubMed:15322419 ]
    5. Williard RL, Middaugh LD, Zhu HJ, Patrick KS: Methylphenidate and its ethanol transesterification metabolite ethylphenidate: brain disposition, monoamine transporters and motor activity. Behav Pharmacol. 2007 Feb;18(1):39-51. [PubMed:17218796 ]
    6. Chuhan YS, Taukulis HK: Impairment of single-trial memory formation by oral methylphenidate in the rat. Neurobiol Learn Mem. 2006 Mar;85(2):125-31. Epub 2005 Oct 24. [PubMed:16246598 ]
    7. Gray JD, Punsoni M, Tabori NE, Melton JT, Fanslow V, Ward MJ, Zupan B, Menzer D, Rice J, Drake CT, Romeo RD, Brake WG, Torres-Reveron A, Milner TA: Methylphenidate administration to juvenile rats alters brain areas involved in cognition, motivated behaviors, appetite, and stress. J Neurosci. 2007 Jul 4;27(27):7196-207. [PubMed:17611273 ]
    8. Sandoval V, Riddle EL, Ugarte YV, Hanson GR, Fleckenstein AE: Methamphetamine-induced rapid and reversible changes in dopamine transporter function: an in vitro model. J Neurosci. 2001 Feb 15;21(4):1413-9. [PubMed:11160413 ]
    9. Tatsumi M, Groshan K, Blakely RD, Richelson E: Pharmacological profile of antidepressants and related compounds at human monoamine transporters. Eur J Pharmacol. 1997 Dec 11;340(2-3):249-58. [PubMed:9537821 ]
    10. Tilley MR, Gu HH: The effects of methylphenidate on knockin mice with a methylphenidate-resistant dopamine transporter. J Pharmacol Exp Ther. 2008 Nov;327(2):554-60. doi: 10.1124/jpet.108.141713. Epub 2008 Aug 12. [PubMed:18698001 ]
    General function:
    Involved in neurotransmitter:sodium symporter activity
    Specific function:
    Serotonin transporter whose primary function in the central nervous system involves the regulation of serotonergic signaling via transport of serotonin molecules from the synaptic cleft back into the pre-synaptic terminal for re-utilization. Plays a key role in mediating regulation of the availability of serotonin to other receptors of serotonergic systems. Terminates the action of serotonin and recycles it in a sodium-dependent manner.
    Gene Name:
    SLC6A4
    Uniprot ID:
    P31645
    Molecular weight:
    70324.165
    References
    1. Dresel SH, Kung MP, Huang X, Plossl K, Hou C, Shiue CY, Karp J, Kung HF: In vivo imaging of serotonin transporters with [99mTc]TRODAT-1 in nonhuman primates. Eur J Nucl Med. 1999 Apr;26(4):342-7. [PubMed:10199939 ]
    2. Izenwasser S, Coy AE, Ladenheim B, Loeloff RJ, Cadet JL, French D: Chronic methylphenidate alters locomotor activity and dopamine transporters differently from cocaine. Eur J Pharmacol. 1999 Jun 4;373(2-3):187-93. [PubMed:10414438 ]
    3. Stehouwer JS, Jarkas N, Zeng F, Voll RJ, Williams L, Owens MJ, Votaw JR, Goodman MM: Synthesis, radiosynthesis, and biological evaluation of carbon-11 labeled 2beta-carbomethoxy-3beta-(3-((Z)-2-haloethenyl)phenyl)nortropanes: candidate radioligands for in vivo imaging of the serotonin transporter with positron emission tomography. J Med Chem. 2006 Nov 16;49(23):6760-7. [PubMed:17154506 ]

    PMID: 19737537

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